Administration of anti-inflammatory steroid results in profound effects on collagen metabolism. The effect of this class of therapeutic agents on collagen metabolism may be affected by decreasing prolyl hydroxylase. This enzyme is responsible for the hydroxylation of certain prolyl residues in collagen peptides to form hydroxyproline, an amino acid found almost exclusively in collagen. Administration of triamcinolone diacetate to rats results in a decrease of prolyl hydroxylase. Treatment with anti-inflammatory steroids may ultimately result in either secretion of underhydroxylated collagen, a decreased secretion of collagen and (or) a feedback inhibition of collagen polypeptide synthesis, if indeed prolyl hydroxylase is the rate limiting enzyme in collagen biosynthesis. Studies done thus far and future investigations are aimed at determining the importance of glucocorticoid mediated alteration of the prolyl hydroxylase in the overall effects of this class of drugs on collagen metabolism in both normal and diseased tissues. We propose to determine the effects of glucocorticoids (using the synthetic steroid triamcinolone as a model compound) on the synthesis, secretion and degradation of collagen. Studies will be carried out to determine molecular mechanisms of alterations of prolyl hydroxylase and possibly collagen polypeptide synthesis. Thus, in the future we may initiate studies to either block or mimic the effects of this class of drugs on collagen metabolism. BIBLIOGRAPHIC REFERENCE: R. A. Wehr, J. G. Smith, D. F. Counts and K. R. Cutroneo. Vitamin A Prevention of triamcinolone diacetate effects on granuloma growth: lack of effect on prolyl hydroxylase. Proc. Soc. Exptl. Biol. and Med. 152:411-414 (1976).